孟德尔和多基因风险因素在阿拉伯乳腺癌患者的相互作用
Mohammed Al-Jumaan1, Hoyin Chu2,3, Abdullah Alsulaiman1
1College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
Genome medicine
|September 1, 2023
概括
这项研究研究了阿拉伯土著人口的乳腺癌遗传学,发现多基因风险评分 (PRS) 预测了家族史和早期发病. 常见的遗传变异有助于早期发病的乳腺癌,独立于罕见的致病变异.
科学领域:
- 基因组学就是基因组学.
- 癌症研究 癌症研究
- 人口遗传学 人口遗传学
背景情况:
- 土著阿拉伯乳腺癌患者比西方同行更早出现.
- 在癌症基因组学研究中,这一群体的代表性不足.
- 多基因和门德尔风险在早期发病中的作用尚不清楚.
研究的目的:
- 调查多基因和罕见变异对阿拉伯土著妇女早期乳腺癌的贡献.
- 为这个研究不足的人群建立基因组风险评估框架.
主要方法:
- 在220名阿拉伯乳腺癌患者的低通全基因组测序 (lpWGS) 和全外体测序 (WES).
- 归算种群特异变异和计算多基因风险得分 (PRS).
- 评估变体的致病性和与家族病史和发病年龄的关联.
主要成果:
- lpWGS变体归算显示出与外体数据的高度一致.
- 调整后的PRS显著与一级相对乳腺癌史相关 (斯皮尔曼rho=0.43,p=0.03).
- 在有家族病史的患者中,更高的PRS与早期乳腺癌呈现的年龄相关.
结论:
- 开发了一个使用lpWGS在未研究的人群中进行多基因风险评估的框架.
- 确定常见变体风险作为早期乳腺癌的一个因素,独立于致病变体状态.
- 强调为了解乳腺癌病因学,人口特异性基因组研究的重要性.
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